RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining PSC 833 with a chemotherapy drug may reduce resistance to the drug and allow more tumor cells to be killed. PURPOSE: Phase I trial to study the effectiveness of liposomal doxorubicin and PSC 833 in treating patients who have AIDS -related Kaposi's sarcoma or other advanced cancers.

Condition	Treatment or Intervention	Phase
epidemic Kaposi's sarcoma recurrent Kaposi's sarcoma unspecified adult solid tumor, protocol specific	Drug: doxorubicin HCl liposome  Drug: PSC 833	Phase I

Further Study Details: 

OBJECTIVES: I. Evaluate the safety profile and tolerability of doxorubicin HCl liposome (Doxil) and PSC 833 in patients with AIDS-related Kaposi's sarcoma and other advanced malignancies. II. Determine the maximum tolerated dose of Doxil when administered with PSC 833 in this patient population. III. Determine the dose-limiting toxicity of Doxil when administered with PSC 833 in this patient population. IV. Determine the effects of PSC 833 on Doxil pharmacokinetics.

PROTOCOL OUTLINE: This is a dose-escalation study of doxorubicin HCl liposome (Doxil). Patients receive Doxil IV over 1 hour on day 1 of each course. During the second and subsequent courses, patients also receive a loading dose of PSC 833 IV over 2 hours and a maintenance dose of PSC 833 IV over 72 hours beginning 15 minutes after completion of Doxil infusion. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. The first seven cohorts of patients receive standard-dose Doxil. The eighth and ninth cohorts of 3-6 patients each receive escalating doses of Doxil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 12-18 patients will be accrued for this study within 12-18 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven Kaposi's sarcoma with 10 or more mucocutaneous lesions or a visceral lesion with at least 2 assessable cutaneous lesions OR Histologically confirmed advanced malignancy that is refractory to standard treatment or for which no standard therapy exists

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior interferon
• Chemotherapy: At least 4 weeks since prior cytotoxic chemotherapy; Prior doxorubicin HCl liposome allowed; No other concurrent cytotoxic chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 4 weeks since prior radiotherapy or external beam therapy; No concurrent palliative radiotherapy
• Surgery: Not specified
• Other: No concurrent medications known to interact with cyclosporine

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: More than 4 months
• Hematopoietic: Neutrophil count at least 1,000/mm3; Platelet count at least 75,000/mm3; Hemoglobin at least 8 g/dL
• Hepatic: Bilirubin less than 1.5 times normal; SGOT no greater than 2 times normal
• Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 50 mL/min
• Cardiovascular: No clinically significant congestive heart failure
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No active opportunistic infections requiring antibiotic treatment; No moderate to severe sensory and motor peripheral neuropathy; No other prior or concurrent malignancy except carcinoma in situ of the cervix or nonmelanoma skin cancer; No hypersensitivity to doxorubicin HCl liposome or cyclosporine

Missouri
      Washington University Barnard Cancer Center, Saint Louis,  Missouri,  63110,  United States

Study chairs or principal investigators

Paula M. Fracasso,  Study Chair,  Washington University Barnard Cancer Center   

Study ID Numbers:  CDR0000066062; WU-106; NCI-T97-0073
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003207
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08